Obesity is a common disease caused by multiple factors and is accompanied by many complications such as hyperlipidemia, fatty liver, arteriosclerosis, cardiovascular disease, hypertension, diabetes, or the like. Recently, obesity is becoming a severe social problem as the diet is westernized. As if to reflect this, the World Health Organization (WHO) defined obesity as one of chronic diseases in 1997.
Obesity is a direct or indirect cause of many adult diseases, including diabetes, hypertension, hyperlipidemia, cholelithiasis, etc. It is a severe problem in that it can be fatal physically or mentally and may cause tremendous sociological or economic losses.
The WHO has warned that the current overweight or obese populations reaching 1 billion will increase by 50% to 1.5 billion in 2015 and will be a major concern of health (Sep. 22, 2005). Overweight and obesity are major risk factors of cardiovascular disease, the number one cause of death in the world. Each year, more than 170 million people die of cardiovascular disease, about 80% among them in the United States and other developed countries. The WHO analyzes that the obesity, which has been considered only as the developed countries' problem, is spreading worldwide with increased fat, salt or sugar in foods, lack of physical activity, development in transportation, or the like. Actually, the countries where 75% or more of the women aged 30 or more are overweight include the United States, Egypt, Mexico, South Africa and Turkey, and the countries where 75% or more of the men aged 30 or more are overweight include the United Kingdom, Argentina, Germany, Greece, Kuwait and New Zeeland.
Also, reporting that the increase of the overweight and obese population is really surprising, the WHO predicts that the rapid increase of the overweight or obese population, particularly in underdeveloped countries, will be a major cause of increased chronic diseases within 10-20 years if no measure is taken.
The main treatment for obesity consists of dieting, physical exercise and drug therapy. According to clinical results, those who received drug therapy along with dieting and physical exercise experienced about 2 times more body weight loss in two years than those who underwent dieting and physical exercise only. Further, they also showed marked improvement in blood pressure, blood sugar and cholesterol.
Accordingly, interest in drug therapy and development of obesity therapeutic agent is increasing.
Anti-obesity drugs inhibit obesity by suppressing appetite, promoting metabolism or inhibiting absorption of specific nutrients in foods. As the structure and function of melanocortins and anorectic peptides known to have appetite suppressing effect, such as bombesin, are known, the development of anti-obesity drug is facing an important turning point.
At present, typical anti-obesity medications are sibutramine (brand name: Reductil, Meridia in USA) and orlistat (brand name: Xenical, Alli). Sibutramine inhibits reuptake of serotonin and noradrenaline, neurotransmitters involved in regulation of appetite, therefore decreasing appetite. However, frequently encountered side effects are dry mouth, paradoxically increased appetite, nausea, strange taste in the mouth, upset stomach, constipation, trouble sleeping, dizziness, drowsiness, menstrual cramps/pain, headache, joint/muscle pain, or the like. Sibutramine can substantially increase blood pressure and pulse in some patients. Therefore regular monitoring needs to be performed. The following side effects are infrequent but serious and require immediate medical attention: cardiac arrhythmias, paresthesia, mental/mood changes, or the like. In addition, careful monitoring is needed as the safety issue of sudden death, heart failure, kidney failure, gastrointestinal disorder, etc. is raised. Furthermore, because such a general appetite suppressant affects the metabolism of proteins and carbohydrates, as well as fats, selective weight loss is impossible. Orlistat treats obesity by reducing intestinal fat absorption. It is marketed as Xenical, but has side effects such as steatorrhea, intestinal gas production, abdominal swelling, or the like, and has limited effect on those who go on a low-fat diet.
Other medications for suppressing appetite are developed, but most of them are associated with mental side effects.
Throughout this specification, a number of literatures and patent documents are referenced and cited. The disclosure of the cited literatures and patent documents are incorporated herein to more clearly explain the background art and the present invention.